Two new patients with acromesomelic dysplasia, PRKG2 type-identification and characterization of the first missense variant.

Abstract

Acromesomelic dysplasia, PRKG2 type (AMDP, MIM 619636), is an extremely rare autosomal recessive skeletal dysplasia characterized by severe disproportionate short stature presenting with acromesomelia, mild metaphyseal widening of the long bones and mild spondylar dysplasia. To date, only four variants have been reported; one nonsense, one splice-site, and two frameshifts in five AMDP families. Here, we report the first missense variant and a second splice-site variant in PRKG2 in two patients with clinical and radiological features of acromesomelic dysplasia. Furthermore, functional studies of the novel missense variant, p.Val470Gly, revealed that it was unable to down-regulate FGF2-induced MAPK signaling and, thus, would be predicted to cause growth delay. Hence, this report expands the mutational spectrum in skeletal dysplasias associated with PRKG2 variants. In addition, we propose recognizable facial features with acromesomelic dysplasia, PRKG2 type.

• Authors: Ozlem Akgun-Dogan, Francisca Díaz-González, Alexander Augusto de Lima Jorge, Neslihan Onenli-Mungan, Nathalia Liberatoscioli Menezes Andrade, Laurana de Polli Cellin, Serdar Ceylaner, Maria Barcellos Rosa Modkovski, Yasemin Alanay, Karen E Heath
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) (Oct 04 2023) ISSN: 1476-5438 [Electronic] England
• PMID: 37789084 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to European Society of Human Genetics.